Stickler syndrome is a dominant osteochondrodysplasia associated with mutations in any one of the three genes encoding the polypeptide subunits of type XI collagen: COL2A1, COL11A1, and COL11A2. In order to better understand the pathogenesis of sensorineural hearing loss caused by mutations in these genes, we have examined the expression of Col11a1 and Col11a2 within the inner ears of mice. The results demonstrate diffuse expression within the soft tissue elements of the inner ear and vestibular labyrinth. We have also characterized mouse models harboring mutations in these genes in order to define their contribution to development of the inner ear and auditory system. Our results demonstrate that mice carrying homozygous functional null mutations for either Col11a1 or Col11a2 do not manifest obvious structural abnormalities of the cochlea. We conclude that mutations in these collagen genes likely alter the biomechanical properties of the cochlea and its neurosensory organs, thus leading to altered sound mechanotransduction and sensorineural hearing loss. We are planning to test this hypothesis in humans using audiologic and electrophysiologic techniques.